Human progesterone receptor A and B isoforms in CHO cells. II. Comparison of binding, transactivation and ed50 values of several synthetic (anti)progestagens in vitro in CHO and MCF-7 cells and in vivo in rabbits and rats

摘要: The human progesterone receptor A and B isoforms (hPR-A hPR-B) were stably transfected in Chinese Hamster Ovary (CHO) cells the presence or absence of mouse mamma tumor virus (MMTV) promoter luciferase (LUC) reporter gene. In this way four CHO cell lines, i.e. hPR-A, hPR-B, hPR-A-MMTV-LUC hPR-B-MMTV-LUC cells, prepared. hPR-A -B compared by binding transactivation analysis for 14 progestagens 7 antiprogestagens. Thereby Org 2058 was used as standard both agonistic assays 31710 antagonistic assays. obtained data with relative affinities (RBA) -B, which are present breast MCF-7 biopotency estimations McPhail tests rabbits ovulation inhibition pregnancy interruption rats. antiprogestagens towards hPR-B hPR-A/B either highly correlated respect to ranking. This also shown high correlation coefficients between RBA's (r = 0.983) those hPR A/B 0.957). showed no differences lines exception 32704 33766 antiprogestagen 33245. Therefore only activities (RAA) (RANTA) RBA values showing a similarity ranking tested compounds, r 0.91 0.97, respectively. Remarkably, 1.6 fold higher than RAA's RANTA's. These vitro RBA, RAA RANTA checked their pharmacological relevance vivo measurements potencies appeared be very predictive on endometrium proliferation test 0.81 0.87, while rats less well 0.516 0.65. On other hand, antiprogestagenic found had good all tested, being 0.849 0.744, conclusion, compounds containing general resemblance. studies indicated that fairly identical could pre-screening (anti)-progestagenic bioactivity rabbits, assay can replace Moreover, direct agonists, antagonists partial is even possible bioassay, making particular class chemical valuable tool studies.